The primary outcome for the study is change in muscle strength from baseline to six months in muscle strength as assessed by MVICT using a fixed testing system. [ Time Frame: 13 months ] [ Designated as safety issue: No ]

For six months, half of patients are randomized into placebo . After 6 months, all patients are on treatment.

Drug: Placebo

For six months, pts are randomized into placebo or treatment. After 6 months, all pts are on treatment

Active Comparator: 1b

Cohort 1b patients are randomized onto treatment. After 6 months, all patients are on drug.

Drug: Valproic Acid (VPA)

Drug: Valproic Acid and Levocarnitine; capsules

Other Names:

Depakote

Carnitor

Detailed Description:

Participation in this study entails six visits and seven to eight blood draws over 13 months. Each visit entails a stay of two days and one night at the General Clinical Research Center (GCRC).

Subjects who live within driving distance will be allowed to participate in the study without an overnight stay through two consecutive outpatient visits. All subjects will be evaluated at two screening visits 2-4 weeks apart to determine eligibility for participation. Eligible subjects will be randomized to receive VPA or placebo for the first six months. At the six-month visit, patients will be evaluated and crossed over to the other regimen.

Eligibility

Ages Eligible for Study:

18 Years to 60 Years (Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Ambulatory adults with SMA 3 ages 18-60. The diagnosis of SMA must be documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder. Patients must be able to walk thirty feet without assistance (i.e. no canes, walkers).

Interest in participating and the ability to meet the study requirements.

Women of child bearing age are required to be on birth control or abstain while participating in the study.

Patients who have participated in a treatment trial for SMA in the 3 months prior to this trial, or plan on enrolling in any other treatment trial during the duration of this trial.

Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing.

Patients with a need for non-invasive ventilatory support (e.g. BiPAP) for > 12 hours/day

Use of medications or supplements which interfere with VPA metabolism and increase the potential risks of the medications, or are hypothesized to have a beneficial effect in SMA animal models or human neuromuscular disorders within 3 months of study enrollment. These agents include riluzole, creatine, butyrate derivatives, growth hormone, anabolic steroids, daily albuterol use, anticonvulsants, or other HDAC inhibitors.

Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481013

Locations

United States, Ohio

Ohio State University Medical Center, Dept. of Neurology

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

University of Utah

Families of Spinal Muscular Atrophy

Abbott

Investigators

Principal Investigator:

John T Kissel

Ohio State University

Study Director:

Sandra P Reyna, M.D.

Families of Spinal Muscular Atrophy

Principal Investigator:

Kathryn J Swoboda, M.D.

University of Utah

More Information

Responsible Party:

Kathryn Swoboda, Associate Professor, Neurology and Pediatrics, University of Utah